Host: The Japanese Society of Toxicology
Quantitative risk assessment methods for chemicals, particularly environmental pollutants and industrial chemicals, have advanced significantly over the last 20 years. In the past, a hundred of safety factor for the most case of derivation of acceptable daily intake has been simply applied to a NOAEL for chronic animal study. New approaches (ex. use of various toxicological endpoints other than chronic effects or use of interspecies difference factors in pharmacokinetics) have been introduced to dose response assessment for derivation of health-based guidance values. A benchmark dose (BMD) approach as one of the new approaches, has been used to for establishing a POD, which can be replaced replace the NOAEL in case of no NOAEL establishment. The BMD approach is also being used to derive a POD for the risk assessment of genotoxic carcinogens. Although universal softwares (BMDS and PROAST) are available as internationally standardized software for calculating BMDL, there is no harmonized procedures on which mathematical model should be selected for BMDL calculation by using such software. And this non-harmonized BMD calculation method is considered to be a barrier for the active use of BMD in other government agencies. We have established the optimal and conservative application criteria of BMD method for administrative use. Recently, model averaging methods for BMDL calculation are becoming the mainstream instead of single mathematical model selection, although new problems have emerged. As for the risk assessment of a large number of chemical substances for which toxicity test information, the TTC concept is useful for administrative management. Although noncarcinogenic TTC is less widely used than carcinogenic TTC, we were able to propose an application guidance for the evaluation of leachable substances from food equipment and containers by using the TTC concept. In this presentation, in addition to introducing research on the development of methods for applying the BMD approach and the TTC concept to administrative use, I would like to discuss how we can improve derivation of the quantitative assessment values, such as health-based guidance values.
